[show abstract][hide abstract] ABSTRACT: Malariometric parameters are often primary endpoints of efficacy trials of malaria vaccine candidates. This study aims to describe the epidemiology of malaria prior to the conduct of a series of drug and vaccine trials in a rural area of Burkina Faso.
Malaria incidence was prospectively evaluated over one year follow-up among two cohorts of children aged 0-5 years living in the Saponé health district. The parents of 1089 children comprising a passive case detection cohort were encouraged to seek care from the local health clinic at any time their child felt sick. Among this cohort, 555 children were randomly selected for inclusion in an active surveillance sub-cohort evaluated for clinical malaria during twice weekly home visits. Malaria prevalence was evaluated by cross-sectional survey during the low and high transmission seasons.
Number of episodes per child ranged from 0 to 6 per year. Cumulative incidence was 67.4% in the passive and 86.2% in the active cohort and was highest among children 0-1 years. Clinical malaria prevalence was 9.8% in the low and 13.0% in the high season (p>0.05). Median days to first malaria episode ranged from 187 (95% CI 180-193) among children 0-1 years to 228 (95% CI 212, 242) among children 4-5 years. The alternative parasite thresholds for the malaria case definition that achieved optimal sensitivity and specificity (70-80%) were 3150 parasites/µl in the high and 1350 parasites/µl in the low season.
Clinical malaria burden was highest among the youngest age group children, who may represent the most appropriate target population for malaria vaccine candidate development. The pyrogenic threshold of parasitaemia varied markedly by season, suggesting a value for alternative parasitaemia levels in the malaria case defintion. Regional epidemiology of malaria described, Sapone area field centers are positioned for future conduct of malaria vaccine trials.
PLoS ONE 01/2013; 8(1):e50036. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Ad35.CS.01 is a pre-erythrocytic malaria candidate vaccine. It is a codon optimized nucleotide sequence representing the P. falciparum circumsporozoite (CS) surface antigen inserted in a replication deficient Adenovirus 35 backbone. A Phase 1a trial has been conducted in the USA in naïve adults and showed that the vaccine was safe. The aim of this study is to assess the safety and immunogenicity of ascending dosages in sub Saharan Africa.
A double blind, randomized, controlled, dose escalation, phase Ib trial was conducted in a rural area of Balonghin, the Saponé health district (Burkina Faso). Forty-eight healthy adults aged 18-45 years were randomized into 4 cohorts of 12 to receive three vaccine doses (day 0, 28 and 84) of 10(9), 10(10), 5X10(10), 10(11) vp of Ad35.CS.01 or normal saline by intra muscular injection. Subjects were monitored carefully during the 14 days following each vaccination for non serious adverse events. Severe and serious adverse events were collected throughout the participant study duration (12 months from the first vaccination). Humoral and cellular immune responses were measured on study days 0, 28, 56, 84, 112 and 140.
Of the forty-eight subjects enrolled, forty-four (91.7%) received all three scheduled vaccine doses. Local reactions, all of mild severity, occurred in thirteen (27.1%) subjects. Severe (grade 3) laboratory abnormalities occurred in five (10.4%) subjects. One serious adverse event was reported and attributed to infection judged unrelated to vaccine. The vaccine induced both antibody titers and CD8 T cells producing IFNγ and TNFα with specificity to CS while eliciting modest neutralizing antibody responses against Ad35.
Study vaccine Ad35.CS.01 at four different dose levels was well-tolerated and modestly immunogenic in this population. These results suggest that Ad35.CS.01 should be further investigated for preliminary efficacy in human challenge models and as part of heterologous prime-boost vaccination strategies.
ClinicalTrials.gov NCT01018459 http://clinicaltrials.gov/ct2/show/NCT01018459.
PLoS ONE 01/2013; 8(11):e78679. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGOUND: Treatment of confirmed malaria patients with Artemisinin-based Combination Therapy (ACT) at remote areas is the goal of many anti-malaria programs. Introduction of effective and affordable malaria Rapid Diagnosis Test (RDT) in remote areas could be an alternative tool for malaria case management. This study aimed to assess performance of the OptiMAL dipstick for rapid malaria diagnosis in children under five.
Malaria symptomatic and asymptomatic children were recruited in a passive manner in two community clinics (CCs). Malaria diagnosis by microscopy and RDT were performed. Performance of the tests was determined.
RDT showed similar ability (61.2%) to accurately diagnose malaria as microscopy (61.1%). OptiMAL showed a high level of sensitivity and specificity, compared with microscopy, during both transmission seasons (high & low), with a sensitivity of 92.9% vs. 74.9% and a specificity of 77.2% vs. 87.5%.
By improving the performance of the test through accurate and continuous quality control of the device in the field, OptiMAL could be suitable for use at CCs for the management and control of malaria.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Genetic factors play a key role in determining resistance/susceptibility to infectious disease. Susceptibility of the human host to malaria infection has been reported to be influenced by genetic factors, which could be confounders if not taken into account in the assessment of the efficacy of interventions against malaria. This study aimed to assess the relationship between haemoglobin genotypes and malaria in children under five years in a site being characterized for future malaria vaccine trials. METHODS: The study population consisted of 452 children living in four rural villages. Hb genotype was determined at enrolment. Clinical malaria incidence was evaluated over a one-year period using combined active and passive surveillance. Prevalence of infection was evaluated via bi-annual cross-sectional surveys. At each follow-up visit, children received a brief clinical examination and thick and thin blood films were prepared for malaria diagnosis. A clinical malaria was defined as Plasmodium falciparum parasitaemia >2,500 parasites/ul and axillary temperature [greater than or equal to]37.5degreesC or reported fever over the previous 24 hours. RESULTS: Frequencies of Hb genotypes were 73.2% AA; 15.0% AC; 8.2% AS; 2.2% CC; 1.1% CS and 0.2% SS. Prevalence of infection at enrolment ranged from 61.9%-54.1% among AA, AC and AS children. After one year follow-up, clinical malaria incidence (95% CI) (episodes per person-year) was 1.9 (1.7-2.0) in AA, 1.6 (1.4-2.1) in AC, and 1.7 (1.4-2.0) in AS children. AC genotype was associated with lower incidence of clinical malaria relative to AA genotype among children aged 1-2 years [rate ratio (95% CI) 0.66 (0.42-1.05)] and 2-3 years [rate ratio (95% CI) 0.37 (0.18-0.75)]; an association of opposite direction was however apparent among children aged 3-4 years. AS genotype was associated with lower incidence of clinical malaria relative to AA genotype among children aged 2-3 years [rate ratio (95% CI) 0.63 (0.40-1.01)]. CONCLUSIONS: In this cohort of children, AC or AS genotype was associated with lower risk of clinical malaria relative to AA genotype only among children aged one to three years. It would be advisable for clinical studies of malaria in endemic regions to consider haemoglobin gene differences as a potentially important confounder, particularly among younger children.
[show abstract][hide abstract] ABSTRACT: Asexual blood stages antigens of malaria parasites are critical in the development of protective immunity. It's believed that protection against malaria involves mainly humoral immune responses elicited by pre-erythrocytic and blood-stage antigens. Study aimed to investigate seasonal variation and risk of clinical malaria episodes to selected P. falciparum antigens in study population. 529 children were visited during two cross sectional surveys (January 2007 and September 2007). 5 mL of venous blood were obtained from each child during each visit to measure antibody levels by ELISA. Children were then actively followed up clinically to record the malaria episodes. Blood smears were made when child had fever or history of fever to assess parasite load and malaria infection prevalence. Antibody levels against assessed antigens increased faster in older children than in younger. No evidence of an association between the levels of antibody and parasite density was noticed. Strong seasonal variation in antibody levels for the majority of the antigens was noticed. Only antibodies to LSA1 and AS155.4 were associated with protection against clinical malaria. Seasonal variation was noticed for all assessed antigens, but few of them were reported to play a protective role.
[show abstract][hide abstract] ABSTRACT: Abstract: The aim of this study was to evaluate the in vitro antiplasmodial activities of four plants used in
traditional medicine. Hydroethanolic extract, hydroacetonic extract and aqueous extract of Mitragyna inermis
(Willd.) O. Kuntze (Rubiaceae), Combretum sericeum G. Don (Combretaceae), Alternanthera pungens H.B.
and K (Amaranthaceae) and Ampelocissus grantii (Baker) Planch (Vitaceae) have been tested in vitro against
chloroquine-resistant strain (K1) and chloroquine-sensitve strain (3D7) of Plasmodium falciparum using pLDH
assay. Aqueous extracts exhibited the best results against K1 with the 50% inhibitory concentration (IC50)
values of 0.54±0.18, 1.72±0.99, 1.54±0.04 :g/mL for respectively, M. inermis leaves, C. sericeum leaves and
whole plant of A. pungens. Hydroethanolic extract from the leaves of M. inermis gave also IC50 value of
0.87±0.10 :g/mL with 3D7. Extracts showed antiplasmodial activity against both chloroquine-sensitive and
chloroquine-resistant P. falciparum strains. Our study justifies the use of these plants in traditional medicine
and leads to further investigations.
Current Research Journal of Biological Sciences. 05/2011; 3(3):216-222.
[show abstract][hide abstract] ABSTRACT: The aim of the study is to investigate through traditional medicinal plants the possibility for discovery and development of new active and safe antimalarial drugs. For ecological reasons, bark of trunk of Zanthoxylum zanthoxyloides instead to roots was used by traditional healers in Burkina Faso to treat malaria or fever and recent study showed that crude alkaloid extract from the bark of trunk displayed good antiplasmodial activity. The bio-guided chromatographic fractionation of this crude alkaloid extract with solvents yielded 11 semi purified fractions which were tested for their antiplasmodial activity and cytotoxicity, respectively against Plasmodium falciparum W<SUB>2</SUB> strains and K562S cells maintained in continuous culture and using flow cytometer. Non polar fractions 2, 3 and 4 displayed good antiplasmodial activity with IC<SUB>50</SUB> ranging from 1.91 to 4.32 μg mL<SUP>-1</SUP> and little toxicity with selectivity index ranging from 3.03 to 6.15. These data allow further investigations in terms of purification, isolation and development of new antiplasmodial compounds from these semi purified fractions and development of improved phytomedicine.
[show abstract][hide abstract] ABSTRACT: In order to prevent the destruction of the ecology and to sustain the flora mainly for medicinal plants, we investigated on alternative parts taken from four plants already known to display antiplasmodial activities and largely used by traditional healers in sub-Saharan Africa. The evaluated parts are bark of trunk for Zanthoxylum zanthoxyloides and leaves for Sarcocephalus latifolius instead of roots, and leaves for Combretum molle and Anogeissus leiocarpus instead of stem bark. The antiplasmodial activity of extracts of these plants was evaluated in vitro using the multi-resistant strain (W2) of Plasmodium falciparum. Antiproliferative activity was also assessed, using K562S human monocyte cell lines, along with calculation of the selectivity index (SI) of each extract. The highest in vitro antiplasmodial activity was found in the alkaloid extract of trunk bark from Z. zanthoxyloides and from the MeOH extract of A. leiocarpus leaves (IC(50) = 1.2 microg/mL and 4.9 microg/mL, respectively) with good selectivity index. Moderate activity was found in the MeOH extract (IC(50) = 5.7 microg/mL) and MeOH/H2O extract (IC(50) = 7.9 microg/mL) of C. molle leaves. Moderate activity was also found in the MeOH/H20 extract (IC(50) = 5.2 microg/mL) and the decoction (IC(50) = 8.2 microg/mL) from leaves of A. leiocarpus. No good activity was found with extracts from roots of S. latifolius. All extracts tested displayed low levels of cytotoxicity against K562S cells. The data generated clearly show that the trunk bark for Z. zanthoxyloides and the leaves for A. leiocarpus and C. molle could be used for the treatment of malaria instead of roots and stem bark.
Parasitology Research 11/2009; 106(2):335-40. · 2.85 Impact Factor
[show abstract][hide abstract] ABSTRACT: The chemical composition of total alkaloids from leaves and roots of Guiera senegalensis was investigated. Three beta-carboline alkaloids were purified: in addition to harman and tetrahydroharman, known in roots and leaves, harmalan (dihydroharman) was isolated for the first time from roots of Guiera senegalensis. Guieranone A, a naphthyl butenone, was also purified from leaves and roots. The in vitro antiplasmodial activity and the cytotoxicity of extracts and pure compounds were evaluated. Each total alkaloid extract and beta-carboline alkaloids presented an interesting antiplasmodial activity associated with a low cytotoxicity. Harmalan was less active than harman and tetrahydroharman. Guieranone A showed a strong antiplasmodial activity associated with a high cytotoxicity toward human monocytes. Its cytotoxicity was performed against two cancer cell lines and normal skin fibroblasts in order to study its anticancer potential: guieranone A presented a strong cytotoxicity against each cell strains. Finally, we evaluated the potent synergistic antimalarial interaction between Guiera senegalensis and two plants commonly associated in traditional remedies: Mitragyna inermis and Pavetta crassipes. Three associations evaluated were additive. A synergistic effect was shown between total alkaloids extracted from leaves of Guiera senegalensis and those of Mitragyna inermis. This result justified the traditional use of the plants in combination to treat malaria.
Journal of Ethnopharmacology 07/2006; 106(2):173-8. · 2.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: In the course of the search for new antimalarial compounds, a study of plants traditionally used against malaria in Burkina Faso was made. An ethnobotanical study permitted the identification of plants currently used by the traditional healers and herbalists. Two plants among them were selected for further study: Pavetta crassipes (K. Schum) and Acanthospermum hispidum (DC). Alkaloid extracts of these plants were tested in vitro against two reference clones of Plasmodium falciparum: the W2 chloroquine-resistant and the D6 chloroquine-sensitive strains. Significant inhibitory activity was observed with Pavetta crassipes (IC(50)=1.23 microg/ml) and A. hispidum (IC(50)=5.02 microg/ml). Antiplasmodial activity was also evaluated against six Plasmodium falciparum isolates from children between 4 and 10 years old. The IC(50) values for the alkaloid extracts were in the range 25-670 ng/ml. These results indicated that P. falciparum wild strains were more sensitive to the alkaloid extracts than strains maintained in continuous culture. Moreover, the alkaloid extracts exhibit good in vitro antimalarial activity and weak cytotoxicity against three human cell lines (THP1, normal melanocytes, HTB-66). Isolation and structural determination are now necessary in order to precisely determine the active compounds.
Parasitology Research 08/2003; 90(4):314-7. · 2.85 Impact Factor
[show abstract][hide abstract] ABSTRACT: In Burkina Faso, most people in particular, in rural areas, use traditional medicine and medicinal plants to treat usual diseases. In the course of new antimalarial compounds, an ethnobotanical survey has been conducted in different regions. Seven plants, often cited by traditional practitioners and not chemically investigated, have been selected for an antiplasmodial screening: Pavetta crassipes (K. Schum), Acanthospermum hispidum (DC), Terminalia macroptera (Guill. et Perr), Cassia siamea (Lam), Ficus sycomorus (L), Fadogia agrestis (Schweinf. Ex Hiern) and Crossopteryx febrifuga (AFZ. Ex G. Don) Benth. Basic, chloroform, methanol, water-methanol and aqueous crude extracts have been prepared and tested on Plasmodium falciparum chloroquine-resistant W2 strain. A significant activity has been observed with alkaloid extract of P. crassipes (IC(50)<4 microg/ml), of A. hispidum, C. febrifuga, and F. agrestis (4<IC(50)<10 microg/ml). The best result is obtained with aqueous extract of T. macroptera with an IC(50)=1 microg/ml. These results confirm the traditional use of these plants.
Journal of Ethnopharmacology 06/2003; 86(2-3):143-7. · 2.76 Impact Factor
[show abstract][hide abstract] ABSTRACT: Insecticide-treated bednets and curtains have been shown to be successful in reducing malaria transmission and child mortality in Africa over periods of up to 2 years. A major concern relating to this approach is that, in time, it will be compromised by the selection of mosquito genotypes that are resistant at the biochemical or behavioural level. We report entomological data from a large area in Burkina Faso where insecticide-treated curtains have been in use for up to 5 years. Longitudinal indoor and outdoor CDC light-trap catches were performed in 4 sentinel villages. In addition cross-sectional surveys using indoor spray catches and outdoor CDC light-trap catches were performed each September in a larger number of villages, including 8 located outside the intervention area. We found no evidence of the selection of mosquito phenotypes that might compromise the intervention. Indoor and outdoor vector densities remained very low after 5 years of intervention, both compared with pre-intervention levels and with concurrent levels outside the intervention area. We found no evidence of a switch to outdoor rather than indoor biting. The proportion of blood meals taken on humans may have decreased but our data are inconclusive on this point. We observed higher vector densities and sporozoite rates at the periphery of the intervention zone than at the centre, which may reflect re-invasion of peripheral villages by mosquitoes from outside the intervention area. In 'real life' programmes, with perhaps patchy, less than optimal coverage, the protection against malaria transmission provided to individuals using insecticide-treated materials may be less than that achieved in the randomized controlled trials which demonstrated an impact of insecticide-treated materials on child mortality.
Transactions of the Royal Society of Tropical Medicine and Hygiene 01/2001; 95(4):353-60. · 1.82 Impact Factor
[show abstract][hide abstract] ABSTRACT: Swartzia madagascariensis , Combretum glutinosum and Tinospora bakis are three plants of the folk medicine used by healers in Burkina Faso for the treatment of malaria. A scientific validation of this utilization was not previously made. Aqueous, methanol, hydromethanol extracts from the roots bark of S. madagascariensis, methanol and hydromethanol extracts from the leaves of C. glutinosum and aqueous and alkaloidal extracts from the roots of T. bakis were also made and their antimalarial activity was screened against Plasmodium falciparum chloroquine-resistant strain W2 in vitro. The screening showed that the methanol and hydromethanol extracts of Swartzia madagascariensis, hydromethanol extracts of Combretum glutinosum and alkaloidal extracts of Tinospora bakis were active(5μg/ml < IC50 < 50 μg/ml).
African Journal of Traditional, Complementary and Alternative Medicines (ISSN: 0189-6016) Vol 3 Num 1.